Antiviral CD8+ T cell effector activities in situ are regulated by target cell type

Cytotoxic T lymphocytes (CTLs) play a prominent role in the resolution of viral infections through their capacity both to mediate contact-dependent lysis of infected cells and to release soluble proinflammatory cytokines and chemokines. The factors controlling these antiviral effector activities in vivo at infection sites are ill defined. Using a mouse model of influenza infection, we observed that the expression of CTL effector activity in the infected lungs is dictated by the target cell type encountered. CD45(+) lung infiltrating inflammatory mononuclear cells, particularly CD11c(hi) dendritic cells, trigger both CTL cytotoxicity and release of inflammatory mediators, whereas CD45(-) influenza-infected respiratory epithelial cells stimulate only CTL cytotoxicity. CTL proinflammatory mediator release is modulated by co-stimulatory ligands (CD80 and CD86) expressed by the CD45(+) inflammatory cells. These findings suggest novel mechanisms of control of CTL effector activity and have potentially important implications for the control of excess pulmonary inflammation and immuno-pathology while preserving optimal viral clearance during respiratory virus infections.